The overall objective of this research is to determine the 3D structures of intact and fragmented immunoglobulins (Igs) to interpret the structural information in terms of antibody function. The research plan involves crystallography, immunology, biochemistry and theoretical computations of molecular dynamics and conformational energies. The specific aims are: 1) To obtain detailed structural parameters of Igs. Rhe, a V(L) dimer, will be refined to about 1.2 angstrom resolution to obtain the most accurate Ig domain parameters to date and to determine the anisotropic thermal factors. Bencedones protein Pav will be refined to about 2.7 angstrom resolution in order to investigate the interactions stabilizing its Fab-like conformation. Precise domain-domain parameters will be defined for use in structural comparisons and for qunatifying relative domain movements. Sequence and 3D variability will be tested as criteria for generalizing structural features from one protein to another. 2) To compute energies and dynamics of Igs: The calculations will be used to predict anisotropic thermal motion, conformational transformations, and effects of hapten binding on protein dynamics. 3) To study Ab-Ag, Fab-Ag, Fab-hapten complexes crystallographically. The source of the complexes will be hybridoma derived monoclonal antibodies with specificity toward a preselected antigenic determinant on lysozyme or toward two dissimilar haptens. The 3D structures will show the identities and spatial dispositions of the binding residues. These data are significant for simulation of combining sites through chemical synthesis, for testing the hypothesized allosteric mechanisms for triggering the reaction with complement, and for testing the F. F. Richards hypothesis attributing the exclusionary binding process governing the combining site in a polyfunctional antibody cavity to dynamic effects. 4) To do hapten binding studies on Pav and Rhe, 5) To crystallize myeloma protens from classes of unknown structure, and 6) To determine the structure of Bence-Jones protein Len.